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Original Article

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Blood Res 2013; 48(4):

Published online December 31, 2013

https://doi.org/10.5045/br.2013.48.4.266

© The Korean Society of Hematology

Prognostic value of immunohistochemical algorithms in gastrointestinal diffuse large B-cell lymphoma

Hee Sang Hwang1, Dok Hyun Yoon2, Cheolwon Suh2, Chan-Sik Park1, and Jooryung Huh1*

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1Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

2Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

Correspondence to : Correspondence to Jooryung Huh, M.D., Ph.D. Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Seoul 138-736, Korea. Tel: +82-2-3010-4553, Fax: +82-2-472-7898, jrhuh@amc.seoul.kr

Received: September 24, 2013; Accepted: November 14, 2013

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Background

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous clinicopathological entity, and its molecular classification into germinal center B cell-like (GCB) and activated B cell-like (ABC) subtypes using gene expression profile analysis has been shown to have prognostic significance. Recent attempts have been made to find an association between immunohistochemical findings and molecular subgroup, although the clinical utility of immunohistochemical classification remains uncertain.

Methods

The clinicopathological features and follow-up data of 68 cases of surgically resected gastrointestinal DLBCL were analyzed. Using the immunohistochemical findings on tissue microarray, the cases were categorized into GCB and non-GCB subtypes according to the algorithms proposed by Hans, Muris, Choi, and Tally.

Results

The median patient age was 56 years (range, 26-77 years). Of the 68 cases included, 39.7% (27/68) involved the stomach, and 60.3% (41/68) involved the intestines. The GCB and non-GCB groups sorted according to Hans, Choi, and Tally algorithms, but not the Muris algorithm, were closely concordant (Hans vs. Choi, κ=0.775, P<0.001; Hans vs. Tally, κ=0.724, P<0.001; Choi vs. Tally, κ=0.528, P<0.001). However, there was no prognostic difference between the GCB and non-GCB subtypes, regardless of the algorithm used. On univariate survival analyses, international prognostic index risk group and depth of tumor invasion both had prognostic significance.

Conclusion

The Hans, Choi, and Tally algorithms might represent identical DLBCL subgroups, but this grouping did not correlate with prognosis. Further studies may delineate the association between immunohistochemical subgroups and prognosis.

Keywords Diffuse large B-cell lymphoma, Gastrointestinal tract, Immunohistochemistry, Prognosis

Article

Original Article

Blood Res 2013; 48(4): 266-273

Published online December 31, 2013 https://doi.org/10.5045/br.2013.48.4.266

Copyright © The Korean Society of Hematology.

Prognostic value of immunohistochemical algorithms in gastrointestinal diffuse large B-cell lymphoma

Hee Sang Hwang1, Dok Hyun Yoon2, Cheolwon Suh2, Chan-Sik Park1, and Jooryung Huh1*

1Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

2Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

Correspondence to:Correspondence to Jooryung Huh, M.D., Ph.D. Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Seoul 138-736, Korea. Tel: +82-2-3010-4553, Fax: +82-2-472-7898, jrhuh@amc.seoul.kr

Received: September 24, 2013; Accepted: November 14, 2013

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous clinicopathological entity, and its molecular classification into germinal center B cell-like (GCB) and activated B cell-like (ABC) subtypes using gene expression profile analysis has been shown to have prognostic significance. Recent attempts have been made to find an association between immunohistochemical findings and molecular subgroup, although the clinical utility of immunohistochemical classification remains uncertain.

Methods

The clinicopathological features and follow-up data of 68 cases of surgically resected gastrointestinal DLBCL were analyzed. Using the immunohistochemical findings on tissue microarray, the cases were categorized into GCB and non-GCB subtypes according to the algorithms proposed by Hans, Muris, Choi, and Tally.

Results

The median patient age was 56 years (range, 26-77 years). Of the 68 cases included, 39.7% (27/68) involved the stomach, and 60.3% (41/68) involved the intestines. The GCB and non-GCB groups sorted according to Hans, Choi, and Tally algorithms, but not the Muris algorithm, were closely concordant (Hans vs. Choi, κ=0.775, P<0.001; Hans vs. Tally, κ=0.724, P<0.001; Choi vs. Tally, κ=0.528, P<0.001). However, there was no prognostic difference between the GCB and non-GCB subtypes, regardless of the algorithm used. On univariate survival analyses, international prognostic index risk group and depth of tumor invasion both had prognostic significance.

Conclusion

The Hans, Choi, and Tally algorithms might represent identical DLBCL subgroups, but this grouping did not correlate with prognosis. Further studies may delineate the association between immunohistochemical subgroups and prognosis.

Keywords: Diffuse large B-cell lymphoma, Gastrointestinal tract, Immunohistochemistry, Prognosis

Fig 1.

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Figure 1.

Examples of partially positive staining for each immunohistochemical marker. (A) CD10 staining showing a positive reaction in a small proportion of the tumor cells (about 20%), which is considered to be a negative result in all 4 algorithms (×100). (B) MUM1 staining exhibiting reactivity in about 40% of tumor cells, which is considered to be positive in the Hans and Tally algorithms but negative in the Choi algorithm (×100). (C) GCET1 positive staining in some tumor cells (about 30%), which is considered to be a negative result in the Choi algorithm (×100). (D) LMO2 positive staining in scattered tumor cells with anaplastic nuclei (about 20%) (×100).

Blood Research 2013; 48: 266-273https://doi.org/10.5045/br.2013.48.4.266

Fig 2.

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Figure 2.

Summary of the (A) Hans, (B) Muris, (C) Choi, and (D) Tally algorithms, and criteria for a positive signal for individual immunohistochemical markers (below or to the right of the white-filled box). Note that the positive criterion for MUM1/IRF4 in the Choi algorithm (more than 80%) is different from that of the other algorithms (more than 30%).

Blood Research 2013; 48: 266-273https://doi.org/10.5045/br.2013.48.4.266

Fig 3.

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Figure 3.

Kaplan-Meier survival analyses with respect to the (A) IPI risk group, (B) depth of tumor invasion and (C) Lugano stage.

Blood Research 2013; 48: 266-273https://doi.org/10.5045/br.2013.48.4.266

Table 1 . Primary antibodies used for immunohistochemical staining and their dilution..


Table 2 . Baseline characteristics of assigned cases (N=68)..

a)Log-rank test. b)Statistically significant parameters..

Abbreviations: IPI, international prognostic index; LDH, lactate dehydrogenase..

Table 3 . Scoring of the different immunohistochemistry stains using individual antibodies..

a)Results according to the Hans algorithm criteria (nuclear staining ≥30%). b)Results according to the Choi algorithm criteria (nuclear staining ≥80%)..

Table 4 . Cross-table analysis of the distribution of the GCB and non-GCB subtypes according to 3 different algorithms..

P<0.001 in all the 3 chi-square analyses..

Abbreviation: GCB, germinal center B-cell-like..

Table 5 . The concordance rate and degrees of agreement between all the 4 algorithms in the gastrointestinal diffuse large B-cell lymphomas..

a)Substantial agreement. b)Moderate agreement..

Table 6 . Immunohistochemistry profiles of discrepant cases: Hans versus Choi algorithms..

Abbreviation: GCB, germinal center B cell-like..

Table 7 . Immunohistochemistry profiles of discrepant cases: Hans versus Tally algorithms..

Abbreviation: GCB, germinal center B cell-like..

Table 8 . Univariate survival analyses of immunohistochemical markers and algorithms..

a)From Lugano stage I to IIE. b)Log-rank test. c)Results according to the criterion for Hans algorithm (nuclear staining ≥30%). d)Results according to the criterion for Choi algorithm (nuclear staining ≥80%). e)Borderline significant parameter (P<0.1)..

Abbreviations: OS, overall survival; PFS, progression-free survival..
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